Although the disease-inducing
role of MOG has been established, its precise function in the CNS remains
obscure.

To gain new insights into the physiological and immunopathological
role of MOG, we determined the 1.8-A crystal structure of the MOG extracellular
domain (MOGED).

MOGED adopts a classical Ig (Ig variable domain) fold that
was observed to form an antiparallel head-to-tail dimer.

A dimeric form
of native MOG was observed, and MOGED was also shown to dimerize in solution,
consistent with the view of MOG acting as a homophilic adhesion receptor.

The MOG35-55 peptide, a major encephalitogenic determinant recognized by
both T cells and demyelinating autoantibodies, is partly occluded within
the dimer interface.

The structure of this key autoantigen suggests a relationship
between the dimeric form of MOG within the myelin sheath and a breakdown
of immunological tolerance to MOG that is observed in multiple sclerosis.